Synthetic iron-oxo “diamond core” mimics structure of key intermediate in methane monooxygenase catalytic cycle

Abstract

Molecular oxygen (O2) is the principal oxidant used by aerobic organisms to carry out a wide range of metabolic reactions and transformations. The enzymes involved in these processes use a rich variety of different active sites to activate O2, such as heme cofactors, mono- and binuclear nonheme iron centers, mono- and binuclear copper complexes, and heteronuclear heme iron/copper clusters (1). Typically, oxygen is activated in a tightly controlled manner to ensure that the formation of the key reactive species in the corresponding catalytic cycle occurs only when the target substrate is present, thereby suppressing potentially harmful side reactions in the enzyme active site (2). A particularly well studied example of an enzyme that follows this general strategy is provided by cytochrome P450 (3). As outlined in Fig. 1 Upper , binding of substrate to the heme-containing active site of cytochrome P450 causes dissociation of the FeIII-bound water ligand, thereby triggering the reduction of the iron center to the reactive FeII state. The FeII species binds and activates O2 to generate an iron(IV)-oxo porphyrin radical intermediate. This highly potent oxidant then proceeds to incorporate one of the O atoms derived from molecular oxygen into a specific C![Graphic][1] H bond of the substrate, in a process that yields the oxidized product and restores the resting FeIII state of the enzyme. High-valent intermediates have also been identified in the catalytic cycles of an increasing number of nonheme diiron enzymes (1, 4), such as methane monooxygenase (MMO) (2, 5). Found in methanotropic bacteria, MMO catalyzes the chemically challenging conversion of methane to methanol (Fig. 1 Lower ), thereby reducing the amount of this greenhouse gas that is being released into the atmosphere by nearly 1 billion tons per year … *E-mail: brunold{at}chem.wisc.edu [1]: /embed/inline-graphic-1.gif